Potent immunogenicity in BRCA 1 ‐mutated patients with high‐grade serous ovarian carcinoma
Journal Of Cellular And Molecular MedicinePeer ReviewedDai Ying +42018Journals
High‐grade serous ovarian carcinomas ( HGSOC s) were among the tumours with an unsatisfactory outcome of immune checkpoint inhibitors ( ICI s). It is imperative to develop feasible biomarker for identifying responsive candidates and guiding precise immunotherapy for HGSOC patients. Here, we analysed genomic data of patients with HGSOC s to depict their immunological phenotype of tumour microenvironment ( TME ) and figure out the major determinants of immunogenicity. In comparison with other solid tumours, we observed the lowest levels of PD ‐L1, total mutation burden ( TMB ) and cytolytic molecules in HGSOC s. Surprisingly, TMB is not certainly positively related to tumour immune response as it failed to predict the response to ICI s in a considerable portion of patients in previous clinical trials. By a machine learning approach in search of biomarkers for immunotherapy implications for HGSOC s, we identified the ten most dominant factors determining the immunogenicity of HGSOC s. Interestingly, we found that BRCA 1 mutated tumours presented a potent immunogenic phenotype, independent of TMB , meeting the criteria of both our dominant factors and the determinants of immunogenicity established before. Our findings provide evidence that BRCA 1‐mutation may be served as a predictive biomarker in guiding ICI therapies for the patients with HGSOC s.
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